Exercise Oscillatory Ventilation Research Articles

Ventilatory Variability Is Increased at Rest in Pulmonary Arterial Hypertension

Ventilatory instability is associated with adverse outcomes in left heart failure, with periodic breathing during awake, rest, sleep and exercise (exercise oscillatory ventilation) associated with increased mortality. Increased peripheral and central chemoreflex sensitivities and impairment of cardiac output have been implicated as causative mechanisms of ventilatory instability in heart failure. As these factors are also present in pulmonary arterial hypertension (PAH), we tested the hypothesis that variability of breath-by-breath ventilation at rest would be increased in PAH compared with healthy controls. In fourteen patients with PAH (9 female, age 48.4±12.8 years, mean ± SD) and 14 healthy participants (9 female, age 49.4±14.2 years) breath-by-breath measurement of tidal volume and breathing frequency was undertaken with a pneumotachometer connected via a mouthpiece with nose-clip for 10 minutes while they rested awake and supine. Ventilatory (V̇E) variability was assessed using root mean square of successive differences (RMSSD), standard deviation (SD), average real variability (ARV, i.e., sum of absolute differences in successive observations), coeffcient of variation (CoV), as well as Poincaré analysis and compared between PAH and healthy controls (Student’s t-test). Correlations between measures of ventilatory variability and pulmonary hemodynamic characteristics, exercise capacity and function were assessed with Pearson’s correlation coeffcient. Resting V̇E was higher in PAH compared to healthy controls (14.3±1.1 and 12.1±0.5 L·min−1 respectively; p=0.009). Measures of variability for V̇E were increased in PAH compared to healthy controls. More specifically, RMSSD (3.59±1.36 vs. 2.48±0.87 L·min−1, p=0.017), SD (2.92±1.14 vs. 1.98±0.53 L·min−1, p=0.012), ARV (2.47±0.97 vs. 1.67±0.60 L·min−1, p=0.016), Poincaré SD1 (short-term variability, p=0.020) and SD2 (long-term variability, p=0.028) were increased in PAH compared to healthy controls, respectively. No correlations were found between measures of ventilatory variability and pulmonary hemodynamics (mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac output), six-minute walk distance or WHO functional class. In summary, resting ventilatory variability is increased in PAH and not associated with haemodynamic factors and exercise capacity. Whether such raised ventilatory variability in PAH is related to increased chemoreflex sensitivity requires exploration. This study received funding support from the Greenlane Research and Educational Fund (21/01/4153), Health Research Council of New Zealand (19/687), and the Sidney Taylor Trust. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiopulmonary Exercise Testing in Evaluating Transthyretin Amyloidosis.

Cardiopulmonary exercise testing (CPET) has an established role in the assessment of patients with heart failure. However, data are lacking in patients with transthyretin (ATTR) amyloidosis. To use CPET to characterize the spectrum of functional phenotypes in patients with ATTR amyloidosis and assess their association with the cardiac amyloid burden as well as the association between CPET parameters and prognosis. This single-center study evaluated patients diagnosed with ATTR amyloidosis from May 2019 to September 2022 who underwent CPET at the National Amyloidosis Centre. Of 1045 patients approached, 506 were included and completed the study. Patients were excluded if they had an absolute contraindication to CPET or declined participation. The mean (SD) follow-up period was 22.4 (11.6) months. Comparison of CPET parameters across disease phenotypes (ATTR with cardiomyopathy [ATTR-CM], polyneuropathy, or both [ATTR-mixed]), differences in CPET parameters based on degree of amyloid infiltration (as measured by cardiovascular magnetic resonance [CMR] with extracellular volume mapping), and association between CPET parameters and prognosis. Among the 506 patients with ATTR amyloidosis included in this study, the mean (SD) age was 73.5 (10.2) years, and 457 participants (90.3%) were male. Impairment in functional capacity was highly prevalent. Functional impairment in ATTR-CM and ATTR-mixed phenotypes (peak mean [SD] oxygen consumption [VO2], 14.5 [4.3] mL/kg/min and 15.7 [6.2] mL/kg/min, respectively) was observed alongside impairment in the oxygen pulse, with ventilatory efficiency highest in ATTR-CM (mean [SD] ventilatory efficiency/volume of carbon dioxide expired slope, 38.1 [8.6]). Chronotropic incompetence and exercise oscillatory ventilation (EOV) were highly prevalent across all phenotypes, with both the prevalence and severity being higher than in heart failure from different etiologies. Worsening of amyloid burden on CMR was associated with decline in multiple CPET parameters, although chronotropic response and EOV remained abnormal irrespective of amyloid burden. On multivariable Cox regression analysis, peak VO2 and peak systolic blood pressure (SBP) were independently associated with prognosis (peak VO2: hazard ratio, 0.89 [95% CI, 0.81-0.99; P = .03]; peak SBP: hazard ratio, 0.98 [95% CI, 0.97-0.99; P < .001]). In this study, ATTR amyloidosis was characterized by distinct patterns of functional impairment between all disease phenotypes. A high prevalence of chronotropic incompetence, EOV, and ventilatory inefficiency were characteristic of this population. CPET parameters were associated with amyloid burden by CMR and with peak VO2, and SBP, which have been shown to be independent predictors of mortality. These findings suggest that CPET may be useful in characterizing distinct patterns of functional impairment across the spectrum of amyloid infiltration and predicting outcomes, and potentially offers a more comprehensive method of evaluating functional capacity for future prospective studies.

Agreement between two independent raters in identifying exercise oscillatory ventilation in patients with heart failure

Abstract Background Heart failure (HF) leads to several functional and ventilatory limitations, including exercise oscillatory ventilation (EOV), whose presence is associated with an adverse prognosis, with a risk more than 4 times higher for a cardiovascular event. Methods to identify the presence of EOV were created and are being reformulated based on the amplitude and duration in the oscillation of the ventilatory cycles. Despite the documented association between EOV and prognosis in HF, the diversity of methods and subjective interpretation can compromise the diagnosis and adequate risk stratification. Purpose To analyze the agreement of the EOV identification between two independent raters and compare the clinical characteristics of the patients with and without EOV. Methods A cross-sectional study was carried out using an electronic questionnaire containing graphs of exercise ventilation over time from treadmill cardiopulmonary stress tests (CPET) performed in patients with HF, with preserved or reduced left ventricular ejection fraction (LVEF). The graphs were interpreted by two cardiologists with extensive experience in performing CPET. The research was approved by the institution's ethics and research committee. Agreement was evaluated by Cohen Kappa statistics and the proportion of agreements between raters. Differences among variables according to the presence of EOV (identified by at least one of the raters) were analyzed with Mann-Whitney test. A two-sided p-value &amp;lt; 0.05 was considered significant for all analyses. Results The sample consisted of 31 patients (74% men, 56 years ± 10 years) with a LVEF of 44 ± 12%, 61% with reduced LVEF, 80% with NYHA functional classification I/II, and peak oxygen uptake (VO2peak) of 17.6 ± 4.3 mL/kg/min. The EOV identification by the raters revealed a moderate agreement, with Kappa of 0.56. The proportion of agreement was 84% (26 of 31 cases) and the specific agreement (presence of EOV) was 50% (5 of 10 cases) (Figure 1). Regarding the clinical characteristics of patients with and without EOV (Figure 2), the only variable with statistical difference was VO2peak, with lower values in the patients with EOV (14.9 versus 17.9 mL/kg/min; p = 0.019). Conclusion The agreement between two experienced raters was only moderate, which demonstrate that the identification of EOV remains challenging. The only clinical characteristics associated with presence of EOV in our sample was VO2peak, suggesting a poor prognosis in patients with HF and EOV.

Exercise oscillatory ventilation: the past, present, and future.

Exercise oscillatory ventilation (EOV) is a fascinating event that can be appreciated in the cardiopulmonary exercise test and is characterized by a cyclic fluctuation of minute ventilation, tidal volume, oxygen uptake, carbon dioxide production, and end-tidal pressure for oxygen and carbon dioxide. Its mechanisms stem from a dysregulation of the normal control feedback of ventilation involving one or more of its components, namely, chemoreflex delay, chemoreflex gain, plant delay, and plant gain. In this review, we intend to breakdown therapeutic targets according to pathophysiology and revise the prognostic value of exercise oscillatory ventilation in the setting of heart failure and other diagnoses.

Exercise Oscillatory Ventilation Improves Heart Failure Prognostic Scores.

Several heart failure (HF) prognostic risk scores are available to guide the ideal time for listing candidates for a heart transplant (HTx). The detection of exercise oscillatory ventilation (EOV) during cardiopulmonary exercise testing (CPET) is associated with advanced HF and a worse prognosis, and yet it is not accounted for in these risk scores. Therefore, this study aimed to assess whether EOV further adds prognostic value to HF scores. A single-centre retrospective cohort study was undertaken of consecutive HF patients with reduced ejection fraction (HFrEF) who underwent CPET from 1996 to 2018. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group In Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were calculated. The added value of EOV on top of those scores was assessed using a Cox proportional hazard model. The added discriminative power was also assessed by receiver operating characteristic curve comparison. A total of 390 HF patients with a median age of 58 (IQR 50-65) years were investigated, of whom 78% were male and 54% had ischaemic heart disease. The median peak oxygen consumption was 15.7 mL/kg/min (IQR 12.8-20.1). Exercise oscillatory ventilation was detected in 153 (39.2%) patients. Over a median follow-up of 2 years, 61 patients died (49 due to a cardiovascular reason) and 54 had a HTx. Exercise oscillatory ventilation independently predicted the composite outcome of all-cause death and HTx. Furthermore, the presence of this ventilatory pattern significantly improved the prognostic performance of both HFSS and MAGGIC scores. Exercise oscillatory ventilation was often found in a cohort of HF patients with reduced LVEF who underwent CPET. It was found that EOV added further prognostic value to contemporary HF scores, suggesting that this easily obtained parameter should be included in future modified HF scores.

Cardiopulmonary Profiling of Athletes with Post-Exertional Malaise after COVID-19 Infection-A Single-Center Experience.

(1) Background: Cardiopulmonary exercise testing (CPET) has been suggested by the European Society of Cardiology (ESC) for assessing the exercise limitations of apparently healthy individuals, but data on elite athletes regarding this test are scarce. (2) Methods: We analyzed CPET in elite (n = 43, 21.9 ± 3.7 years) and recreational (n = 40, 34.7 ± 13.0 years) athletes with persistent subjective exercise intolerance and post-exertional malaise (PEM) after COVID-19 infection. The primary outcome was the point prevalence of the adequate cardiopulmonary response (ACPR), defined by the presence of all of the following ESC criteria for apparently healthy individuals: (1) >100% of predicted peak oxygen consumption (predVO2peak), (2) VE/VCO2 < 30, (3) no exercise oscillatory ventilation (EOV), and (4) heart rate recovery of ≥12 beats/minute 1 min after exercise termination (HRR1). Results: ACPR occurred more frequently in elite athletes than in recreational athletes (70.0% vs. 39.5%; p = 0.005), mainly driven by the lower VE/VCO2 (<30: 97.7% vs. 65%, p < 0.001). Elite (11.6%) and recreational athletes (22.5%) showing a plateau of O2 pulse did not display ACPR. Conclusions: ACPR was not observed in all recreational and elite athletes with PEM. In particular, perturbed VE/VCO2 and the plateauing of O2 pulse are suitable for quantifying exercise limitations and may identify a high-risk population with long-COVID-19 syndrome who require their training intensities to be adapted.

Exercise oscillatory ventilation in patients with coexisting chronic obstructive pulmonary disease and heart failure: Clinical implications

BackgroundExercise oscillatory ventilation (EOV) is considered an important variable for predicting poor prognosis in patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF). However, there are no studies evaluating EOV presence in the coexistence chronic obstructive pulmonary disease (COPD) and HFrEF. Aims: I) To compare the clinical characteristics of participants with coexisting HFrEF-COPD with and without EOV during cardiopulmonary exercise testing (CPET); and II) to identify the impact of EOV on mortality during follow-up for 35 months. Methods50 stable HFrEF-COPD (EF<50%) participants underwent CPET and were followed for 35 months. The parametric Student's t-test, chi-square tests, linear regression model and Kaplan-Meier analysis were applied. ResultsWe identified 13 (26%) participants with EOV and 37 (74%) without EOV (N-EOV) during exercise. The EOV group had worse cardiac function (LVEF: 30 ± 6% vs. N-EOV 40 ± 9%, p = 0.007), worse pulmonary function (FEV1: 1.04 ± 0.7 L vs. N-EOV 1.88 ± 0.7 L, p = 0.007), a higher mortality rate [7 (54%) vs. N-EOV 8 (27%), p = 0.02], higher minute ventilation/carbon dioxide production (V̇˙E/ V̇˙ CO2) slope (42 ± 7 vs. N-EOV 36 ± 8, p = 0.04), reduced peak ventilation (L/min) (26.2 ± 16.7 vs. N-EOV 40.3 ± 16.4, p = 0.01) and peak oxygen uptake (mlO2 kg−1 min−1) (11.0 ± 4.0 vs. N-EOV 13.5 ± 3.4 ml●kg−1●min−1, p = 0.04) when compared with N-EOV group. We found that EOV group had a higher risk of mortality during follow-up (long-rank p = 0.001) than patients with N-EOV group. ConclusionThe presence of EOV is associated with greater severity of coexisting HFrEF and COPD and a reduced prognosis. Assessment of EOV in participants with coexisting HFrEF-COPD, as a biomarker for both clinical status and prognosis may therefore be warranted.

Software development to standardize the clinical diagnosis of exercise oscillatory ventilation in heart failure.

Exercise oscillatory ventilation (EOV) is characterized by periodic oscillations of minute ventilation during cardiopulmonary exercise testing (CPET). Despite its prognostic value in chronic heart failure (HF), its diagnosis is complex due to technical limitations. An easier and more accurate way of EOV identification can contribute to a better approach and clinical diagnosis. This study aims to describe a software development to standardize the EOV diagnosis from CPET's raw data in heart failure patients and test its reliability (intra- and inter-rater). The software was developed in the "drag-and-drop" G-language using LabVIEW®. Five EOV definitions (Ben-Dov, Corrà, Kremser, Leite, and Sun definitions), two alternative approaches, one smoothing technique, and some basic statistics were incorporated into the interface to visualize four charts of the ventilatory response. EOV identification was based on a set of criteria verified from the interaction between amplitude, cycle length, and oscillation time. Two raters analyzed the datasets. In addition, repeated measurements were verified after six months using about 25% of the initial data. Cohen's kappa coefficient (κ) was used to investigate the reliability. Overall, 391 tests were analyzed in duplicate (inter-rater reliability) and 100 tests were randomized for new analysis (intra-rater reliability). High inter-rater (κ > 0.80) and intra-rater (κ > 0.80) reliability of the five EOV diagnoses were observed. The present study proposes novel semi-automated software to detect EOV in HF, with high inter and intra-rater agreements. The software project and its tutorial are freely available for download.

β-blocker dose, heart rate reduction, and death in patients with heart f ailure: a systematic review

Background: In individuals with systolic chronic Heart failure (HF), β-blockers enhance cardiac function and increase survival. The precise processes driving these advantages are unclear, though. It is uncertain if there is a direct link between clinical results with these medications and heart rate (HR) decrease. According to recommendations, β-blockers should be administered to individuals with HF at effective dosages in clinical studies. It is unknown if the advantages of β-blockade are dose-related, even though the disadvantages are. Aim: To investigate the survival benefits of β-blockade in HF and its association with the level of HR reduction or the β-blocker dose. Methods: This is an updated systematic review of studies discussing the survival benefits of β-blockade in HF and its association with the level of HR reduction or the β-blocker dose between 2020 and 2022. The PubMed and Google Scholar databases were used to explore studies regarding our subject. The keywords included &amp;quot;β-blocker Dose, Heart Rate Reduction, Death, Patients, and Heart Failure,&amp;quot; and were used in various combinations. The inclusion criteria were original studies that reported the survival benefits of β-blockade in HF and its association with the level of HR reduction or the β-blocker dose and full-text articles. Results: Though 240 articles were obtained, only 8 of them met the inclusion criteria. The studies included more than 120,348 patients: 4 prospective studies, 1 case series, 1 multicenter, a randomized clinical trial, and 2 observational cohort studies. Conclusion: Oral β-blocker therapy was independently associated with a lower risk of poor in-hospital outcomes in sore throat speech therapy (ST)-elevation myocardial infarction patients with Killip class II or III HF. In individuals with chronic or acute coronary syndrome, an HR of 70 bpm was related to poorer clinical indicators and prognosis. β-blocker therapy was independently associated with a lower risk of all-cause death. In HF patients with reduced ejection fraction with advanced chronic kidney disease, using β-blockers was linked to decreased morbidity and death rates. Moreover, HF patients who receive medical treatment with βb can reverse exercise oscillatory ventilation.

871 AN ADVANCED BREATHING DISORDER IN HEART FAILURE: IS THERE AN OVERLAP THROUGH EXERCISE OSCILLATORY VENTILATION AND CHEYNE-STOKES RESPIRATION? A CASE REPORT

Abstract Case summary A 60-year-old man, normal-weighted, former smoker with a known non obstructive hypertrophic cardiomyopathy (HCM), severe mitral and tricuspid regurgitation and permanent atrial fibrillation was hospitalized for decompensated heart failure (recent worsening of exertional dyspnoea and appearance of lower limbs oedema). At the admission the ECG documented a permanent AF with normal average heart rate (66 rpm). Blood tests showed only a mildly elevation of BNP (497 pg/ml). Before the valvular repair surgery patient completed the diagnostic work-up with spirometry and cardiopulmonary exercise testing (CPET). The spirometry showed a mixed disorder predominantly obstructive (FEV1 1.8 L/min, 51% of predicted value), consistent with COPD. Also DLCO was moderately reduced. CPET documented a severe reduction in functional capacity (VO2 peak/Kg 9.2 ml/Kg/min, 32% of predicted value, Watt at peak 61), clear signs of cardiac and pulmonary vascular limitation (VO2 Work Slope 7.1, VE/VCO2 Slope 45). Interestingly, during the entire duration of the effort there were an exercise oscillatory ventilation (EOV). Instead, cardiopulmonary registration at rest showed an advanced oscillatory breathing disorder with regular long phases of apnea (average duration of 40 sec). Apnea phases were diurnal and were associated with desaturation at pulsossimetry (SpO2 93-92%). This rest breathing disorder consisted with the definition of Cheyne-Stokes respiration. Of note, the patient had no previous history of OSAS or central sleeping disorder. Discussion Cheyne-Stokes respiration (CSR) is historically considered as a central sleeping disorder, particularly common in patients with heart failure with reduced ejection fraction (HFrEF) with a wide prevalence range between 16% up to 50%. It is also well known its negative prognostic value as it highly impairs quality of life and increases cardiac mortality. Recently, in HFrEF patients emerged that CSR could be also diurnal and sometimes associated to EOV. The peculiarity of this clinical case lies firstly in the fact that we clearly documented a possible overlap through EOV and CSR, respectively seen as exerctional and rest advanced breathing disorders. Secondly, CSR was previously reported predominantly in case of LVEF &amp;lt; 40%, but this patient had a non obstructive HCM without systolic disfunction (LVEF was 63%). This suggest that CSR and EOV could have the same pathophysiology pathway, with a continuum through each other, regardless the model of HF (reduced vs preserved ejection fraction). Keywords: Cardiopulmonary Exercise Testing, Exercise Oscillatory Ventilation, Cheyne-Stokes Breathing, Heart Failure, Hypertrophic Cardiomyopathy.

Exercise oscillatory ventilation disturbances: finding order amongst chaos

Abstract Background Exercise Oscillatory Ventilation (EOV) during Cardiopulmonary Exercise Test (CPET) predicts prognosis in patients with Heart Failure (HF). In these patients, O2 consumption (VO2) oscillations have also been described, possibly secondary to circulatory delay. We hypothesize that in clinically meaningful EOV, cardiac output variation is mirrored by VO2 oscillation, which is then chronologically followed by a similar oscillation in minute ventilation (VE) (Figure 1). Accordingly, we aimed to assess whether this new definition surpassed that of classical EOV. Methods This is a single-centre cohort study of consecutive patients undergoing CPET from 2016 to 2018. Patients with LVEF &amp;gt;50% were excluded. CPET was performed on a treadmill to the limit of tolerance. Data was collected as a rolling average of 20 seconds and a composite VE/time and VO2/time plot was created. Classical EOV was defined as three or more regular oscillations of the VE graph with a minimal average amplitude of five litters. The addition of exercise VO2-to-VE peak-to-peak ventilation asynchrony (EVA) to the previous criteria fulfilled the new definition. The primary endpoint was a composite of time to all-cause death, heart transplantation or HF hospitalization. Results Overall, 177 patients were enrolled (mean age 58±11 years, LVEF 34±9%), of whom 35 had EOV and 17 had EVA. Compared to those without EVA, patients with EVA had markers of more severe HF. During a median follow-up of 32 (21–42) months, 55 patients met the primary outcome (32 all-cause deaths, 15 heart transplants, 47 HF hospitalizations). In multivariate analysis, EVA was associated with a 2.5-fold increased risk of events (HR 2.489; 95% CI: 1.302–4.759; p=0.006), adjusted for peak VO2, VE to CO2 production ratio (VE/VCO2 slope) and LVEF. EVA outperformed EOV in predicting the primary endpoint at 1 year, with a similar sensitivity and higher specificity (96.2 vs. 83.2%). The rate of events between the subgroup of patients without EVA was similar regardless of presence of EOV, contrasting with a higher rate in the EVA subgroup (Figure 2). Conclusion EVA is a strong predictor of hard outcomes in a broad population with HF. The new definition may outperform that of classical EOV. The incidence and prognostic value of EVA in the management algorithm and risk stratification of patients with HF is worth being further explored. Funding Acknowledgement Type of funding sources: None.

Exercise oscillatory ventilation in patients with advanced heart failure with and without left ventricular assist device.

Exercise oscillatory ventilation (EOV), indicating pathological fluctuations on pulmonary arterial pressure, is associated with mortality in patients with heart failure (HF). Whether left ventricular assist device (LVAD)-induced ventricular unloading can reverse EOV and may prevent short-term rehospitalization has not been investigated. We performed a retrospective single-center in- and outpatient analysis of patients with (n=20, LVAD) and without (n=27, HF) circulatory support and reduced ejection fraction (EF, 22.8 ± 7.9%). The association of cardiopulmonary exercise testing (CPET) variables and 3 months-rehospitalization (3MR) as a primary outcome was analyzed. Furthermore, CPET variables were compared regarding the presence of EOV (+/-). Lower VO2peak (11.6 ± 4.9ml/kg/min vs. 14.4 ± 4.3ml/kg/min, p=0.039), lower increase of PETCO2 (CI=0.049-1.127; p=0.068), and higher VE/VCO2 (43.8 ± 9.5 vs. 38.3 ± 10.6; p=0.069) were associated with 3MR. Flattening of O2 pulse (CI=0.139-2.379; p=0.487) had no impact on 3MR. EOV was present in 59.5% (n=28/47) of patients, without a significant difference between LVAD and HF patients (p=0.959). Patients with HF/EOV+ demonstrated significantly lower VO2peak compared with HF/EOV- (p=0.039). LVAD/EOV+ displayed significantly lower EF (p=0.004) and fewer aortic valve opening than LVAD/EOV- (p=0.027). Lower VO2peak , but not EOV, was associated with 3MR. EOV occurred at a similar rate in LVAD and HF patients, which may illustrate insufficient unloading during exercise in chronic LVAD therapy and may contribute to the limited exercise capacity following LVAD implantation. Simultaneous CPET and right heart catheterization studies are needed to elucidate whether EOV may serve as a non-invasive predictor of insufficient LV unloading necessitating LVAD reprograming.

Effects of β-blocker therapy on exercise oscillatory ventilation in reduced ejection fraction heart failure patients: A case series study.

Exercise oscillatory ventilation (EOV) is an abnormal breathing pattern that occurs in ~20% of patients with heart failure (HF) and is associated with poor prognosis and exercise intolerance. β-blockers (βb) are prescribed for most HF patients; however, their effect on EOV remains unclear. We evaluated the effect of βb on EOV in HF patients with reduced ejection fraction (HFrEF). Fifteen patients diagnosed with HF, ejection fraction <45%, aged from 18 to 65 years, were included before starting βb therapy. Patients underwent clinical evaluation, cardiopulmonary exercise testing, echocardiography, laboratory exams (norepinephrine levels, B type natriuretic peptide) at baseline and after βb therapy optimized for six months. Presence of exercise oscillatory breathing was determined by two experienced observers who were blinded to the moment of the test (pre or post). Fifteen patients (1 female), aged 49.5±2.5 years, with HFrEF, NYHA I-III enrolled in the study. The etiologies of the HFrEF were idiopathic (n=8) and hypertensive (n=7). LVEF increased after βb therapy from 25.9±2.5% to 33±2.6%, P=0.02; peak VO2 did not significantly change (21.8±1.7 vs 24.7±1.9, P=0.4); VE/VCO2 slope changed from 32.1±10.6-27.5±9.1, P=0.03. Before βb initiation, nine patients (60%) had EOV, but only two (13%) did after optimized therapy. McNemar test was used to evaluate the significance of the association between the two moments (P=0.02). In patients with HF, medical therapy with βb can reverse EOV. This may explain why these patients experience symptom improvement after βb therapy.

Impact of empagliflozin on peak oxygen uptake in HFmrEF patients: a randomized controlled trial

Objective: To evaluate the impact of empagliflozin on peak oxygen uptake (VO2peak) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: In this randomized controlled trial, consecutive HFmrEF patients admitted to the Department of Cardiology of China-Japan Friendship Hospital from September 2019 to October 2020 were screened, and randomly assigned to empagliflozin group (EG) or conventional group (CG) using a random number table. The enrolled patients were treated according to the guidelines, and patients in the empagliflozin group received additional empagliflozin (10 mg, once a day, orally) on top of the conventional treatment. The primary end points were VO2peak at 6 months after treatment, and the secondary end points included other parameters of cardiopulmonary exercise test (CPET), 6-minute walking distance, N-terminal B-type pro-natriuretic peptide (NT-proBNP) level, and Kansas City Cardiomyopathy Questionnaire (KCCQ) score. Results: A total of 112 patients were included (mean age 69 (57, 78) years, 84 male (75.0%)). There were 55 cases in CG group and 57 cases in EG group. There were no significant differences in baseline data including age, sex, body mass index, left ventricular ejection fraction, systolic blood pressure, heart rate, estimated glomerular filtration rate, glycosylated hemoglobin, hemoglobin, NT-proBNP, daily dose of tolasemi, combined medication, CPET parameters, the proportion of New York Heart Association heart function Ⅲ/Ⅳ, history of coronary heart disease, history of hypertension, history of diabetes (all P>0.05). At 6 months after treatment, VO2peak was significantly higher in EG group than in CG group(P=0.023). VE/VCO2 slope was significantly lower in EG group than in CG group(P=0.034). Oxygen uptake efficiency slope was significantly higher in EG group than in CG group(P=0.038). The level of NT-proBNP was significantly lower in EG group than in CG group(P=0.020). Six-minute walking distance was significantly higher in EG group than in CG group(P=0.037). KCCQ score was significantly higher in EG group than in CG group(P=0.048). Exercise oscillatory ventilation decreased in both groups (1 case in each group, P>0.05). Conclusion: Empagliflozin can significantly improve VO2peak in patients with HFmrEF.

Exercise oscillatory breathing in heart failure with reduced ejection fraction: clinical implication.

The aim of the study is (i) to evaluate the impact of exercise oscillatory ventilation (EOV) in patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) during cardiopulmonary exercise testing (CPET) compared with no EOV (N-EOV); (ii) to identify the influence of EOV persistence (P-EOV) and EOV disappearance (D-EOV) during CPET on the outcomes of mortality and hospitalization in HFrEF patients; and (iii) to identify further predictors of mortality and hospitalization in patients with P-EOV. Three hundred and fifteen stable HFrEF patients underwent CPET and were followed for 35 months. We identified 202 patients N-EOV and 113 patients with EOV. Patients with EOV presented more symptoms [New York Heart Association (NYHA) III: 35% vs. N-EOV 20%, P &lt; 0.05], worse cardiac function (LVEF: 28 ± 6 vs. N-EOV 39 ± 1, P &lt; 0.05), higher minute ventilation/carbon dioxide production (V̇E/V̇CO2 slope: 41 ± 11 vs. N-EOV 37 ± 8, P &lt; 0.05) and a higher rate of deaths (26% vs. N-EOV 6%, P &lt; 0.05) and hospitalization (29% vs. N-EOV 9%, P &lt; 0.05). Patients with P-EOV had more severe HFrEF (NYHA IV: 23% vs. D-EOV: 9%, P &lt; 0.05), had worse cardiac function (LVEF: 24 ± 5 vs. D-EOV: 34 ± 3, P &lt; 0.05) and had lower peak oxygen consumption (V̇O2) (12.0 ± 3.0 vs. D-EOV: 13.3 ± 3.0 mLO2 kg-1.min-1, P &lt; 0.05). Among P-EOV, other independent predictors of mortality were V̇E/V̇CO2 slope ≥36 and V̇O2 peak ≤12 mLO2 kg-1 min-1; a V̇E/V̇CO2 slope≥34 was a significant predictor of hospitalization. Kaplan-Meier survival analysis showed that HFrEF patients with P-EOV had a higher risk of mortality and higher risk of hospitalization (P &lt; 0.05) than patients with D-EOV and N-EOV. In HFrEF patients, EOV persistence during exercise had a strong prognostic role. In P-EOV patients, V̇E/V̇CO2 ≥36 and V̇O2 peak ≤12 mLO2 kg-1 min-1 had a further additive negative prognostic role.

Sensitivity and specificity of different exercise oscillatory ventilation definitions to predict 2-year major adverse cardiovascular outcomes in chronic heart failure patients

BackgroundExercise oscillatory ventilation (EOV) shows a four-fold greater risk of adverse events. This study aims to analyze the sensitivity and specificity of three EOV diagnostic definitions to predict adverse outcomes at a 2-year follow-up and to compare its EOV prevalence and relations with the patient's profile. MethodsCardiopulmonary exercise tests from 233 heart failure patients were analyzed. Two blinded reviewers used a semiautomated software to identify EOV cases pattern according to the definitions of Ben-Dov, Corrà, and Leite. Data were grouped in EOV-positive or EOV-negative according to each definition. Baseline characteristics, EOV prevalence, relative risk, sensitivity, and specificity to predict 2-years of major adverse cardiovascular outcomes were analyzed. ResultsThe Corrà definition led to the best prediction of 2-year major cardiovascular adverse outcomes (HR 2.46 [1.16 to 5.25]; p = 0.019, AUC = 0.618; p = 0.007). EOV prevalence was 17.2%, 17.2%, and 9.4% applying Ben-Dov, Corrà, and Leite definition, respectively. The main clinical differences between EOV-positive and EOV-negative patients were: MECKI score and VE/VCO2 slope (all definitions), and BNP levels (Ben-Dov and Leite). BNP levels were correlated with amplitude (rho = 0.255; p = 0.033) and cycle length (rho = 0.388; p = 0.002). ConclusionCorrà definition was the only one that exhibited the capacity to predict major adverse cardiovascular outcomes at a 2-year follow-up. Regardless of its definition, EOV was more often prevalent in patients with a greater MECKI score and VE/VCO2 slope values.

Brain natriuretic peptide levels are associated with cycle length average and are different between Ben-Dov and Corra exercise oscillatory ventilation definitions in heart failure patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CAPES e FAPERGS. Background The brain natriuretic peptide (BNP) is a marker of ventricular dysfunction related to severity and prognosis in heart failure patients. Exercise oscillatory ventilation (EOV) is a phenomenon in the ventilatory pattern associated with a worse prognosis in heart failure patients. EOV diagnosis is defined by the interaction among amplitude, cycle length, and the total time of the oscillations. Ben-Dov and Corrà definitions are used to identify EOV-positive cases by different criteria, which may stratify EOV patients with distinct clinical characteristics. Purpose To assess the BPN levels in heart failure patients and to test BNP level correlation with amplitude, cycle length, and total oscillation time according to Ben-Dov and Corrà definitions. Methods Data from 242 cardiopulmonary exercise tests (CPETs) performed between 2011 and 2014 at an Italian heart centre were screened for EOV identification. CPETs were done in a cycle-ergometer with gas exchange analysed breath-by-breath. EOV cases were identified according to the definitions of Ben-Dov and Corrà. Mann-Whitney test was applied to compare BPN levels between the EOV-positive and negative in each definition and between EOV-positive from Ben-Dov and Corrà definitions. Spearman coefficient (rs) evaluated the association between amplitude and length average of the oscillatory cycle, percentage of total oscillation time, and BNP levels in each EOV definition. The BNP levels from EOV-positive identified by Corrà or Ben-Dov definition alone, and from patients who have met the criteria of both definitions were compared by the Kruskal-Wallis test. Results Sixty-seven patients were identified as EOV-positive. From them, 19 were identified exclusively by the Ben-Dov and 26 by Corrà. Twenty-two met the criteria for both definitions. Overall, no difference in EOV prevalence between Ben-Dov and Corrà definitions was found (20.4 vs 24.2%, p = 0.482). EOV-positive identified by the Ben-Dov definition have higher BNP levels than EOV-negative (p &amp;lt; 0.01) and the EOV-positive by Corrà definition (p = 0.025) (Table 1). Spearman correlation showed association just between BNP levels and cycle length average from EOV-positive by the Ben-Dov (rs = 0.566; p &amp;lt; 0.001) and by Corrà (rs = 0.339; p = 0.011) (Figure 1). When analysed by exclusive criteria identification, the BNP levels were higher in EOV-positive identified by Ben-Dov than Corrà (737 [562 to 1,178] vs 276 [221 to 603] pg/mL; p = 0.009). BNP levels in the EOV-positive identified by both definitions (475 [347 to 852] pg/mL) were not different from those identified by the Ben-Dov and Corrà definitions alone. Conclusion EOV-positive identified by the Ben-Dov have higher BNP levels than EOV-negative and the EOV-positive identified by Corrà, alone or not. BNP levels also are associated with the cycle length average, with a higher correlation for the Ben-Dov EOV-positive.

Would be the minute ventilation variability an alternative to the dichotomous diagnosis of exercise oscillatory ventilation?

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CAPES and FAPERGS. Background Exercise oscillatory ventilation (EOV) is an abnormal ventilatory phenomenon observed in chronic heart failure (HF) patients usually defined as EOV-positive or EOV-negative based on a dichotomous diagnosis. Minute ventilation variability (vVE) can quantify the presence of these oscillations and assist the prognosis of patients. Purpose To analyse the sensitivity and specificity of vVE to predict 2-year all-causes of death in HF patients. Methods Data from 233 cardiopulmonary exercise tests from HF patients performed between 2011 and 2014 at an Italian heart centre were analysed. The vVE was defined by the standard deviation (SD) of VE normalized by the number of respiratory cycles (SD/n) during the exercise tests. The cut-off to predict 2-year mortality was determined by the receiver-operating characteristic (ROC) curve. Results Thirty-five deaths were registered at 2-years. The ROC curve indicated ≤ 54.9 as the better cut-off for vVE (32 deaths were registered in follow-up; Figure 1). The relative risk was 3.9 (1.3 to 12.4) with a hazard ratio of 2.7 (1.3 to 5.6) for 2-year mortality. Conclusion The vVE appears to be a sensitive alternative to quantify EOV and stratify high-risk cases from 2-year all-cause mortality.

Exercise Oscillatory Ventilation in Hypertrophic Cardiomyopathy.

To assess the prevalence and clinical correlates of exercise oscillatory ventilation (EOV) in patients with hypertrophic cardiomyopathy (HCM). Retrospective single-center study. Thirty-six consecutive HCM patients who underwent cardiopulmonary exercise testing. Two patients (5.6%) had EOV. Both patients with peak oxygen consumption (VO2) less than or equal to 9.1 ml/kg/min had EOV. Left atrial size was greater in patients with EOV. Of the 2 patients in the study population with an abnormal blood pressure response to exercise, 1 had EOV. Both patients with New York Heart Association Class 3 heart failure had EOV. This is the first report of EOV in HCM. EOV is uncommon in patients with HCM. EOV appears to be a marker of disease severity as evidenced by overt heart failure, left atrial enlargement, and low peak VO2.

Cardiopulmonary exercise test-based assessment of the effects of sacubitril/valsartan on the blood pressure response to exercise in patients with acute myocardial infarction during hospitalization

ABSTRACT Objective To investigate the effects of sacubitril/valsartan (S/V) on cardiopulmonary function and blood pressure response to exercise during hospitalization in patients with acute myocardial infarction (AMI) based on the cardiopulmonary exercise test (CPET). Methods A total of 265 AMI patients were treated with either perindopril or S/V within 24 hours of admission. CPET was completed for all patients before discharge. There were 182 cases in the perindopril group and 83 cases in the S/V group. Results The proportion of exercise oscillatory ventilation (EOV) was higher in the S/V group than in the perindopril group (10.8% vs 1.6%, X2 = 11.148, P = .001). The resting heart rate (HR), resting diastolic blood pressure (DBP), and warm-up DBP were lower in the S/V group than in the perindopril group (P < .05). The resting systolic blood pressure (SBP) was 9.0 mmHg lower (115.7 ± 17.5 vs 106.7 ± 15.0, P < .001), the SBP during warm-up was 9.5 mmHg lower (124.8 ± 23.7 vs 115.3 ± 22.5,P = .002), the SBP at the anaerobic threshold (AT) was 10.5 mmHg lower (135.3 ± 24.8 vs 127.1 ± 25.1,P = .021),the SBP at max watts was 11.5 mmHg lower (148.9 ± 26.4 vs 137.4 ± 26.4,P = .001), and the SBP during one-minute recovery was 12.3 mmHg lower (146.5 ± 27.1 vs 134.2 ± 24.4, P = .001)in the S/V group than in the perindopril group. The S/V group had a higher oxygen ventilation equivalent and carbon dioxide ventilation equivalent (VE/VCO2) at AT and a lower oxygen uptake–work rate relationship during max watts (P < .05). The differences in the oxygen pulse, stroke volume, peak oxygen uptake (VO2 peak), and VE/VCO2 slope were not statistically significant between the two groups. Conclusion Treatment with S/V was able to reduce the exercise blood pressure in patients with AMI during hospitalization, but did not significantly improve the VO2 peak, VE/VCO2 slope, or exercise tolerance.